胰岛素对糖尿病大鼠认知功能及脑星形胶质细胞GFAP表达的影响

Effects of insulin on cognitive impairment and GFAP expression of cerebral astrocytes in diabetic rats

[目的]观察胰岛素治疗糖尿病大鼠不同时期的空间学习能力变化及脑星形胶质细胞胶质纤维酸性蛋白(glial fibrillary acidic protein,GFAP)表达,探讨胰岛素对大鼠认知功能的影响。[方法]健康成年雄性SD大鼠52只等量随机分入1个月组与3个月组。每组动物再随机分入糖尿病组(10只)、胰岛素组(10只)与对照组(6只)。糖尿病组与胰岛素组以链脲佐菌素(STZ)腹腔注射制备大鼠糖尿病模型;胰岛素组根据血糖水平注射胰岛素。建模成功后分别于1与3个月用Morris水迷宫实验测试大鼠空间学习能力,而后处死,免疫组化法检测海马、尾壳核及脑室旁白质星形胶质细胞GFAP表达情况。[结果]逃避潜伏期在糖尿病组1与3个月时均较对照组延长(P<0.05);与糖尿病组相比,胰岛素组在1个月时缩短(P<0.05),但3个月时无明显差异。GFAP表达在糖尿病组1个月时尾壳核区、海马区增多(P<0.05),3个月时各脑区均增多(P<0.05);与糖尿病组相比,胰岛素组在1个月时尾壳核区、海马区表达减少(P<0.05),但3个月时各脑区均无明显差异。[结论]随着糖尿病病程进展大鼠认知功能损害逐渐加重,同时伴星形胶质细胞反应性增生;胰岛素治疗可适当延缓糖尿病认知功能损害出现时间,但不能阻止其发生。

[Objective] To investigate the effects of insulin on cognitive impairment and GFAP expression of cerebral astrocytes in diabetic rats.[Methods] Fifty-two healthy adult male SD（Sprague-Dawley） rats were randomly divided into group of 1 month（n=26） and group of 3 months（n=26）.The rats in each group were then divided into 3 groups： diabetic group（group A,n=10）,insulin treatment group（group B,n=10） and control group（group C,n=6）.The rats in group A and B were induced to develop diabetes mellitus by intraperitoneal streptozotocin injection.The rats in group B were treated by insulin.Morris water maze were used to detect the cognition of the rats in all groups at 1 and 3 months after the models were successfully formed,and then the GFAP expressions of astrocytes in basal ganglia,hippocampus and white matter nearby lateral ventricle of these rats were detected.[Results] The escape latencies of rats in group A at both 1 and 3 months were significantly longer than those of group C（P〈0.05）.Compared to that in group A,the latency in group B was significantly shorter at 1 month（P〈0.05）,while it was similar at 3 months.The GFAP expression of astrocytes in group A was stronger in basal ganglia and hippocampus at 1 month（P〈0.05）,and in these areas and white matter nearby lateral ventricle at 3 months than those in group C（P〈0.05）.The GFAP expression in group B was weaker than that in group A at 1 month（P〈0.05）,while it was similar at 3 months.[Conclusion] The cognitive impairment increased gradually with the diabetes progression in rats,accompanying with the reactive astrocyte proliferation.The early insulin application could delay the diabetic cognitive impairment,but could not inhibit its occurrence.